In order to anaylze the mechanism underlying cerebral vasospasm after subarachnoid hemorrhage (SAH) and to determine the pharmacological basis for treatment and prophylaxis of the spasm, experiments were carried out in monkey and dog basilar arteries in vivo and in vitro that were exposed to oxyhemoglobin (oxyHb), erythrocyte hemolysate and blood, quite important substances in generating the cerebral vasospasm. The results obtained are as follows. (1) Contractions caused by oxyHb and hemolysate were endothelium-dependent and suppressed by treatment with aspirin, indomethacin and ONO3708, a PG receptor antagonist, but were unaffected by superoxide dismutase and OKY046, a thromboxane A_2 synthesis inhibitor. (2) OxyHb released significant amounts of prostaglandin (PG) E_2 and PGF_<2alpha> into the bathing media, which were measured by immunoradiological method. The stimulated release was depressed by indomethacin. (3) Intracisternal injections of oxyHb or autologous blood produced a basi
… Morelar artery spasm in anesthetized dogs and monkeys that was determined angiographically. The maximal arterial constriction was attained 2 hrs after oxyHb and 7 days after blood ; the magnitudes of constriction were almost identical. (4) Treatment with aspirin prevented the vasospasm caused by oxyHb, whereas OKY046 was ineffective. Ca^<++> entry blockers were also effective in preventing the Hb-induced spasm. (5) Incubation of oxyHb with ascorbic acid abolished the vasospastic actions of oxyHb in isolated and in vivo basilar arteries.The findings obtained so far indicate that basilar artery constrictions caused in vivo and in vitro by oxyHb and hemolysate are associated with vasoconstrictor PGs, but not thromboxane A_2, released mainly from the endothelium. Treatment with cyclooxygenase inhbitors, PG receptor antagonists and Ca^<++> entry blockers or cisternal irrigation with artifical fluids containing ascorbic acid may be clinically effective in preventing the genesis of cerebral vasospasm after SAH. Cerebral vasospasm elicited by intracisternal injections of oxyHb would be a useful model for the analysis of mechanisms underlying delayed vasospasm after SAH.(2)大脳動脈条片の収縮反応は、シクロオキシゲナ-ゼ阻害薬やプロスタグランディン(PG)受容体遮断薬の前処置によって強く抑制されたが、トロンボキサン(TX)A_2合成阻害薬の影響を受けなかった。また、ス-パ-オキシド陰イオンの除去薬やカタラ-ゼによって抑制されなかった。(3)oxyHbの収縮作用は内皮除去によって著名に減弱した。(4)oxyHbは摘出大脳動脈からのPGF_2αとPGE_2の遊離を増大し、その作用は血菅内皮の除去およびシクロオキシゲナ-ゼ阻害薬の処置によって強く抑制された。(5)oxyHbを麻酔イヌおよびサルの大槽内に注入すると、除々に脳底動脈の収縮が現れ、その程度は2時間後に最大となった。収縮の最大値は、自家血を大槽内に注入7日後にみられる収縮の強さと同程度であった。(6)oxyHbによる脳底動脈攣縮は、アスピリンやニカルジピンによって阻止された。アスコルビン酸で処置したoxyHbは、無処理のoxyHbでみられるような血管攣縮をひきおこさなかった。以上のin vivoおよびin vitroの脳動脈を用いた実験より、クモ膜下出血後の脳血管攣縮に最も関係が深いと考えられるoxyHbの脳動脈収縮には、主として内皮細胞からの血管収縮性PGの遊離が関与していると結論される。TxA_2やス-パ-オキシド陰イオンは関与しない。同動脈攣縮の予防には、シクロオキシゲナ-ゼ阻害薬、PG受容体遮断薬およびカルシウム拮抗薬の処置に加えて、アスコルビン酸の脳室内潅流が臨床的にも有効であると考えられる。 Less